The overall objective of this proposal is to investigate the hypothesis that biological aging is related to morphological and biochemical changes in the hypothalamus which result in alterations in hormone levels and possibly thymic innervation which, in turn, affects the age-related decline in immune function. Detailed histologic changes that occur with aging in the hypothalamus of Fisher-344 rats (1 to 29 months) will be determined by light and electron microscopy. In addition, histochemical and fluorescentmicroscopic studies of the thymus will be perfromed to identify age-related alterations in cholinergic and adrenergic innervation. Because it is possible that age-related hypothalamic control of neuroimmunomodulation is mediated by fluctuation in circulating hormones, serum levels of GH, LH, FSH and prolacting will be determined by radioimmunoassay at various ages in animals undergoing detailed histologic study. Concurrently, the effect of hormones upon immunologic reactivity will be assessed by exploring the surface membrane of lymphoid cells of various aged animals for the presence of hormone receptors. The modulatory role of these hormones on antigen- and mitogen-induced lumphocyte reactivity will be determined as a function of age. Changes in the susceptibility of lymphoid cells to hormonal influence and number and/or affinity of receptors will be correlated with age-related fluctuations in hormone levels and morphologic changes in the aging hypothalamus and thymus. Finally, the relationship of the hypothalamus and longevity will be determined utilizing neonatal and mature rats with electrolytic lesions in the anterior hypothalamlus.